Filter device to capture a desired amount of material and methods of use

ABSTRACT

The present invention is a filter device with methods to capture a desired amount of material suspended in a liquid or gas. These filter capture methods may be used for the purification or enrichment of various sample constituents or captured material may be observed or analyzed. The filter device employs a deformable filter to provide a simple reliable device to capture a desired amount of material, with minimal electronic intervention.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. patent application Ser. No.10/263,129, filed on Oct. 2, 2002, and published as United StatesPublished Patent Application No. 2004/0065622 A1, and claims priorityfrom that application.

BACKGROUND OF INVENTION

In industry and biology it is often advantageous to capture particulatematerial suspended in a liquid or gas, on a filter for purification,enrichment, observation or subsequent analysis. The quantity andcharacteristics of particulate material is important in manufacturing,for example, processes that utilize powders, pigments, fuels orlubricants. Particle evaluations are also used to assess contaminants inwater or air such as pollen, asbestos and soot. Particulate material issometimes used indirectly to assess proteins or chemicals, for example,beads coated with monoclonal antibody may be interacted with blood. Thenthese beads may be captured on a filter and assessed for bound protein.

As used herein, “sample suspension” means particulate material suspendedin a liquid or gas. “Material” as used herein means biological cells,organisms, bacteria, viruses, or components of these, as well as organicand inorganic particulates or any other matter which may be captured orisolated on a filter. This captured material may be subsequently used toprovide diagnostic and/or analytical information or be re-suspended orotherwise used. For example, captured material may be analyzedchemically or may be placed on a receiving surface, such as a microscopeslide for analysis.

Although there are a number of established methods to depositmono-layers of material on a receiving surface for observation oranalysis, controlling the amount of material collected on a filter ismore difficult to achieve. Typically, electronic control andintervention is required to monitor and control the collection ofmaterial on a filter apparatus and/or other laboratory methods(employing particle counters and dilution techniques) are used to adjustthe concentration of the material in suspension. Unfortunately, thesemethods require additional apparatus and electronics, and are relativelycomplex or expensive in terms of supplies, and time. Therefore, asimple, reliable method of capturing a desired amount of material on afilter would be advantageous.

The present invention is a filter device that provides a means tocollect a desired amount of material. To accomplish this, a pressuresensor is used substantially to monitor the flow rate through thefilter. In addition, the pressure sensor may be combined with a valvethat provides control over sample flow, and thus the collection ofmaterial. In one embodiment of the present invention, a pressure sensorand valve are integrated to form a pressure-sensitive check valve. Inother embodiments the membrane filter or filter assembly themselvesdeform, acting as a pressure sensor and flow control mechanism.

SUMMARY

It would be beneficial to provide a simple filter apparatus to capture adesired amount of material on a filter that does not rely on relativelycomplex electronics and sensors. In addition, it would be advantageousto provide a filter capture method that can be automated to prepare aplurality of samples, simultaneously. Accordingly, as will be furtherdescribed, the present invention provides a novel apparatusincorporating a pressure transducer and means to substantially halt orotherwise adjust sample flow, providing a simple, reliable device tocapture a desired amount of material without complex electronics. Inaddition, the present invention is easily automated to allow materialfrom a plurality of samples to be captured on a membrane filter,simultaneously.

As previously discussed herein, a variety of pressure sensors areavailable with appropriate characteristics for exploitation within thepresent invention. For some applications material captured on a filteris intended for contract-transfer to a receiving surface, such as amicroscope slide. Accordingly, for some applications when a relativelylarge filter is required, or the suspending fluids are viscous, forexample, a filter support structure may be desirable.

The present invention provides a filter apparatus using means to measureor sense the flow rate of a gas or liquid through a filter. In someembodiments pressure is sensed, however, the flow rate of a fluid or gascould also be sensed. In some embodiments, the present inventionterminates or otherwise adjusts sample flow when a predetermined amountof material has been captured on a filter for example by venting thepressure differential responsible for sample flow, or closing the flowpathway, for example with a valve. In other embodiments of the presentinvention material collection on a filter is substantially reduced byrestricting access to the filter, for example, by changing its positionor deforming its shape.

Filter types include fibrous and mesh membranes, porous and capillaryporous membranes, and fabric and gel lattices, for example. Such filtersare commonly made from paper, nylon, glass fibers, nitrocellulose,polypropylene, chemical gels etc. In some cases filters are furthertreated to enhance certain properties such as capture capacity,flexibility, selectivity or adherence by coating them or incorporatingother compounds such as PTFE or protein binding compounds. Accordingly,filters can be formed in various shapes such as planar, conical,pyramidal, hemispherical, or spherical, or filters may have their shapeimposed by a carrier or other support structure.

BRIEF DESCRIPTION OF THE DRAWINGS

The organization and manner of the structure and operation of thepreferred embodiments of the invention, together with further objectsand advantages thereof, may best be understood by reference to thefollowing description, taken in connection with the accompanyingdrawings, wherein like reference numerals identify like elements inwhich:

FIG. 1 a (Prior art) Method to collect and monitor the concentration ofmaterial captured on a membrane filter.

FIG. 1 b (Prior art) Membrane filter device used in conjunction withFIG. 1.

FIG. 2 a shows an embodiment of the present invention capturing adesired amount of material.

FIG. 2 b shows another embodiment of the present invention capturing adesired amount of particulate material from a fluid suspension.

FIG. 2 c shows the embodiment of FIG. 2 b used to capture a desiredamount of material suspended in a gas.

FIG. 3 a shows a membrane filter apparatus with pressure-sensitive checkvalve.

FIG. 3 b shows another configuration of membrane filter apparatus.

FIG. 3 c shows an embodiment of the present invention, incorporating apressure-sensitive check valve in the form of spring tabs arrangedaround the periphery of a filter apparatus.

FIG. 4 shows an embodiment of the present invention utilized to processa plurality of samples.

FIG. 5 a shows a syringe filter assembly of an embodiment of the presentinvention where a deformable filter provides flow rate monitoring(pressure detection) and flow rate control.

FIG. 5 b shows a desired amount of material collected on the syringefilter associated with FIG. 5 a.

FIG. 6 a show yet another embodiment of a filter assembly to monitor andcontrol or otherwise adjust flow rate through a filter.

FIG. 6 b further describes the filter assembly associated with FIG. 6 a.

FIG. 6 c shows an embodiment of a filter assembly at rest (under normaloperating conditions).

FIG. 6 d shows the filter assembly embodiment of FIG. 6 c in anactivated state having responded to pressure changes indicative ofcollecting a desired amount of material.

DETAILED DESCRIPTION OF THE DRAWINGS AND PREFERRED EMBODIMENTS

While the invention may be susceptible to embodiment in different forms,there is shown in the drawings, and herein will be described in detail,specific embodiments with the understanding that the present disclosureis to be considered an exemplification of the principles of theinvention, and is not intended to limit the invention to that asillustrated and described herein.

FIG. 1 a (prior art) illustrates a system 10 to collect a desiredquantity of cells onto the underside of a screen-type filter 12. Asdiagrammed, a pressure sensor 26 is in communication with both sides ofa membrane filter 12. Accordingly, one side of the membrane 12 in thecollection vessel 18 is shown at ambient pressure with pressure sensor26 provided on the opposite side of the membrane. Pressure unit 30typically responds to electrical control signals from a control unit,which can be microprocessor-controlled, to apply selected fluidconditions to the interior of the collection vessel.

FIG. 1 b (Prior art) further illustrates the collection vessel 18 withscreen-type filter 12 as used in this apparatus, and as described inU.S. Pat. No. 6,010,909 and again in U.S. Pat. No. 6,225,125. In thismanner, a desired quantity of material may be captured.

FIG. 2 a shows an embodiment of the present invention with filterapparatus 205 comprised of filter 215 deposed between a top body member210 and a bottom body member 220. In this instance, open container 235contains sample suspension 230 (e.g. particulate material suspended in aliquid), which is introduced via pickup tube 245. This pickup tube, asrequired or desired, may comprise part of the bottom body member 220 orpickup tube 245 may be a separate member attached to body member 220.The object of the device, which will now be further described, is toprovide a means to monitor or otherwise sense the flow rate of thissample suspension 230 and to provide a means to alter, adjust, halt orotherwise influence that flow rate when indicated by a sensor 250, whichis in communication (mechanically or electro-mechanically) with themeans to control flow. Sample suspension 230 is drawn by application ofpressure from vacuum source 200 therefore providing a means to causesample suspension 230 to flow as further indicated by flow directionalarrow 240, which as diagrammed, is in the inlet port 221 of the pickuptube 245, into the bottom body member 220, through the filter 215, whichis this instance is a membrane filter, through a flow control element212 (in this instance a valve) and then out through the outlet port 211.(In this embodiment, as well as in subsequently-described andillustrated embodiments, vacuum is used to cause the sample suspensionto flow. Other means can be used for this purpose in this and subsequentembodiments, such as gravity or mechanical means such as a pump.)Accordingly, as sample suspension 230 flows in this manner, particulatematerial in the sample suspension 230 begins to be captured by membranefilter 215. Pressure sensor or pressure transducer 250, in this instancecontained substantially within the top body member 210, communicateswith the upper surface of membrane filter 215. This communication isfurther indicated by communication arrow 270. Pressure sensor 250 isalso in communication with flow control element 212 so as to provide ameans to adjust or otherwise control flow when certain pressures aresensed. This communication between pressure sensor 250 and flow controlelement 212 is further indicated by communication arrow 260.Accordingly, a pressure differential is established across the membranefilter 215, thereby providing a means for the pressure sensor 250 tomonitor the flow rate of the sample suspension. As sample continues toflow, and as described in association with the description of prior artin FIGS. 1 and 2, particulate material that is smaller than the poresize of the membrane filter 215 passes through the membrane (to waste orto another vessel—not shown) while material larger than the pore size ofthe membrane filter 215 is captured. Since filter pores provide theactual pathway through a filter, material captured by the membranefilter 215 typically blocks pores, which in turn restricts flow. Whenthe flow rate drops to a certain level, pressure sensor 250 responds (ata predetermined pressure based on the application, filtercharacteristic, amount of desired material etc. as previously describedherein and in the prior art cited), pressure sensor 250 activates and inturn activates flow control element 212. The flow control element 212may halt the flow of sample suspension 230 and hence stop furthercapture of material on the membrane filter 215, which has now capturedthe desired amount of material. While such a valve (flow control element212) could be implemented in various positions of within the filterassembly 205, generally communication with pressure sensor 250 issimpler and provides more options when these two functions arerelatively closely related. Further examples of this will be provided inthe descriptions accompanying FIGS. 2 b and 2 c. Activation of the flowcontrol element 212 may be mechanical, electromechanical or may beaccomplished via further integration of the pressure sensor and valve(as will be further discussed). Similarly, these elements may bephysically separate or may be functionally integrated. For applications,such as monolayer deposition, that may require access to the filter fortouch or other material transfer method, the top body member 210 andbottom body member of filter apparatus 205 are preferably madeseparable, by employing threads or a press-fit assembly, for example.

FIG. 2 b shows another embodiment of the present invention with samplesuspension 230 being drawn through filter 215 by application of vacuum200. In this instance filter 215 is sealed to the bottom of upper bodymember 210, thereby providing access to material captured by membranefilter 215. As diagrammed the sensor 250 is integrated with flow controlelement 213, which in this instance provides flow control using a valveto vent the pressure source 200 through vent port 214 or flow controlvalve 213, rather than adjusting the sample flow pathway, as describedin association with FIG. 2 a. As required, or desired, the vent maysubstantially release the vacuum supplied by source 200 to halt flow, orthe drop in vacuum provided by this venting may be sensed and the vacuumsource, shut off.

FIG. 2 c shows application of the device and configuration of thepresent invention described in association with FIG. 2 b where samplesuspension 221 consists of particulate matter, for example, soot,suspended in a gas, for example air.

FIG. 3 a shows an embodiment of the present invention 300 comprised of ahollow main body 310 and a pressure-sensitive check valve 320 extendinginto the main body 310 so as to communicate with one side of a membranefilter 330, which is attached to the underside of the main body 310. Asdesired, for use in fluids, a protrusion 335 may be provided on thebottom of the main body 310 or may be fashioned appropriately to stopthe membrane filter 330 from contacting the bottom of a sample vessel(not shown) and disrupting flow during use. A vacuum source 360 isprovided for sample aspiration. Initially, the vent portion 340 of thepressure-sensitive check valve 320 is closed and typically, the membranefilter 330 is fresh (free of sample material). To begin collection,vacuum is used to draw sample suspension (not shown) through themembrane filter 330 causing material to collect on the underside of themembrane filter 330. Accordingly, as material collects, the pores becomeoccluded and the rate of flow of sample suspension decreases. Thepressure-sensitive check value 320 monitors flow rate through themembrane filter 320 and when the flow rate falls to a desired level,thus indicating that a desired amount of material has been collected,the pressure-sensitive check valve 320 triggers (at a predeterminedpressure) and sample flow (and material collection) is halted.Descriptions of filter collection systems that utilize electronics toaccomplish a comparable task may be found in U.S. Pat. No. 6,010,909 andU.S. Pat. No. 6,225,125. A portion of this prior art is presented inFIGS. 1 and 2 herein. Although various filters may be employed in such aconfiguration, for preparing cytological samples, the membrane filter330 typically has relatively uniformly-distributed pores of a uniformsize, intended to capture material larger than the pore size, whilepassing particulate material that is small. Approximately half a dozencompanies provide a filter apparatus that is adapted to a syringe(syringe filters).

For one embodiment of the present invention, the sensor portion of thepressure-sensitive check valve 320 has been adjusted to trigger at adesired, predetermined pressure which is established to indicate captureof a desired quantity of material on the bottom surface of the membranefilter 330. As diagrammed, when the pressure-sensitive check valve 320triggers (indicating that a desired amount of material has beencaptured), a pathway is opened which vents off the vacuum, therebystopping the aspiration of sample. While it is one object of the presentinvention to minimize or eliminate electronics that communicate with thepressure transducer or control systems, a battery-powered pressuretransducer and/or valve assembly is consistent with this objective. Asdesired, the pressure-sensitive check valve 320 could be implemented ina variety of other ways so as to monitor and control sample flow, forexample upon triggering it could close a fluid pathway. For biologicalapplications, or when other dangers are present, it may be preferable tovent the vacuum as described, which serves to limit the potential foraerosols.

To simultaneously prepare several samples, vacuum could be provided by astepper-driven syringe, with one syringe for each sample. For higherlevels of automation a vacuum pump and vacuum isolators may bepreferred. Accordingly, material capture by the present invention may betransferred by contacting an appropriate receiving surface. For someapplications, such as machine vision examination of cytological samples,monolayer deposition may be made to the underside of a cover-glass orother relatively thin, uniform material, such as transparent tape,thereby providing material at approximately the same distance from thetop surface to facilitate focus. To provide additional rigidity, thethin receiving surface may be placed or affixed to a second surface asdesired, or required.

FIG. 3 b shows an alternative configuration of present filter device300, this time having upper body portion 315 and lower body portion 316.A membrane filter 330 is shown to be sealed with the formed body byo-rings 325. The upper and lower body portions 315 and 316 are designedso as to join and seal with the o-rings 325, establishing conditions forsample flow to be substantially through the membrane filter 330. Forsome applications, once a desired quantity of material is captured onthe filter, it may be useful to re-suspend this material byback-flushing the filter. Once material is re-suspended, for example,another filter device may be used to isolate a sub-component of thematerial collected. Alternatively, if access to the filter surface isdesired, the upper body 315 and the lower body 316 should be madeseparable using a press-fit, threads or other convenient form ofassembly.

A pressure-sensitive check valve 320 is shown in communication with theupper body portion 315 of the filter 335. Again, flow through themembrane filter 330 decreases with time due to progressive obstructionof the pores by material as it collects. The pressure-sensitive checkvalve 320 senses flow rate therefore, providing a measure of the amountof material captured by the membrane filter 330.

FIG. 3 c shows an embodiment of the present invention having a membranefilter 330 (not shown) attached on the lower surface of the device body310. As described in association with FIG. 3 a, a standoff 335 may beprovided. In this embodiment the pressure-sensitive check valve 370 isintegrated and implemented around the periphery of the apparatus withplastic spring tabs that operate as poppet valves. These are furtherdiagrammed in expanded view. Plastic spring tab 376 has contact area374, tension sealed into vent hole 372 in the wall of the device body310. Although a single poppet valve of this type could function as apressure-sensitive check valve for the intended use, such functionalityhas been implemented using a plurality of plastic poppet valves 370distributed around the periphery of filter device 300. As described inassociation with FIGS. 3 a and 3 b, applied vacuum 360 initiates theflow of sample suspension (not shown) through the membrane filter 330.And as material is captured on the underside of membrane filter 330, thepressure-sensitive poppet valves 370 are in communication with the upperside of the membrane filter 330, so positioned so as to monitor the flowrate of material through the membrane filter 330. The poppet valve(s)are set to trigger at a predetermined pressure to indicate when adesired quantity of material has been collected on the membrane filter330.

As discussed, the pressure-sensitive check valve 370 may be implementedwith one or more contact tabs. Compound valves of this type may beadjusted to trigger or otherwise activate at a predetermined pressure.Similarly, the characteristics of the valve portion may also be madeadjustable, for example, when used as a vent or fluid pathway thediameter of the valve could be adjusted. For some applications orreasons of manufacture, size, operating range, reliability, sensitivity,trigger rate, etc. it may be desirable to distribute a plurality ofthese plastic spring tabs around the periphery of the device, as shown.Such tab(s) may be affixed as separate units, be fabricated as a ring ofunits designed for insertion into the device body or it may bepreferable to establish these pressure-sensitive check valve componentsas part of a molding process. Again, the application, costs and otherfactors may influence implementation.

FIG. 4 shows a configuration of filter devices of the present inventionfor processing a plurality of samples. A vacuum manifold 400 distributesvacuum which is further isolated via vacuum chambers 410. Material insuspension 430 begins to be aspirated into filter device(s) 420.Accordingly, by selecting appropriate components, a plurality of similaror different samples may be processed simultaneously. Alternatively,each station may be established to capture the same amount of material,or different amounts of material as desired, or required.

FIG. 5 a shows a filter device 500 of the present invention with amembrane filter 530 interposed between upper body 510 and lower body520. Sample suspension (not shown) enters through inlet port 525, passesthrough the membrane filter 530 and exits via outlet port 515. In thisinstance, the membrane filter 530 is selected with sufficientdeformability so as to generally conform to the interior surface 535 ofthe upper device body 510 when a desired amount of material (indicatedby the reduced flow rate through the membrane filter 530) has beencaptured. Accordingly, flow is subsequently restricted to a smaller areaof the membrane filter 530, for example a single central fluid pathway,as diagrammed.

FIG. 5 b shows such a filter 530, as described in association with FIG.5 a, having captured a desired amount of material in region 540 andproviding reduced flow through a more restricted area of the filter 545.As desired, sample flow may continue or be allowed to continue, forexample, until area 545 occludes so as to slow or substantially reduceor stop sample flow, as such continuation has no subsequent effect asthe desired amount of material has been captured in area 540 of thefilter. The device may continue to draw sample as desired withoutsubstantially affecting the desired amount of material collected inregion 540. As desired the upper body 315 and lower body 316 may be madeseparable to provide filter access.

FIG. 6 a shows a filter device 600 of the present invention with amembrane filter assembly 650 interposed between upper body 610 and lowerbody 620. Sample suspension (not shown) enters through inlet port 625,passes through the membrane filter assembly 650 and exits via outletport 615. The membrane filter assembly 650 is comprised of a filter 660and surrounding non-porous support structure 655. In this instance, themembrane filter assembly 650 acts as a pressure transducer, respondingto a reduction in flow rate through the filter 660 as particulatematerial collects on the underside of the filter 660. As described inassociation with FIGS. 5 a and 5 b, deformation of the filter, or inthis instance the membrane filter assembly 650, provides the means toalter flow in response to the pressure differential across the membranefilter assembly 650.

FIG. 6 b shows the membrane filter assembly 650 having a filter area 660supported by a surrounding non-porous support structure 655. The supportstructure 655 has striations 665 allowing it to deform in a triggeredmotion when a predetermined pressure is sensed. As described, materialcollecting on the underside of the filter 660 begins to occlude thefilter 660, contributing to a reduction in flow rate through the filter660 and a pressure change across the membrane filter assembly 650. Whena desired amount of material has been collected the support structuretriggers so as to conform to the inner surface as described inassociation with FIG. 5 a or the support structure may contact a valveas described in association with FIGS. 3 a, b and c so as tosubstantially stop sample flow and therefore halt material collection.

FIG. 6 c shows a membrane filter assembly 670 having a filter area 680in surrounding non-porous support structure 675. The support structure675 has striations 685. The membrane assembly is diagrammed in a firststate which is substantially maintained until the pressure differentialacross the membrane filter assembly 670 reaches a predetermined triggerpoint at which time the structure toggles or deforms to a second state.

FIG. 6 d shows the membrane filter assembly 670 as discussed inassociation with FIG. 6 c in a triggered or deformed state. As desiredor required, the membrane filter assembly 670 may itself provide a meansto alter flow when the state toggles, indicating collection of a desiredamount of material on the filter 680. Alternatively, the state changemay contact a valve, a switch or value interfaced to a switch so thatflow through the membrane may be adjusted, or halted.

While preferred embodiments of the present invention are shown anddescribed, it is envisioned that those skilled in the art may devisevarious modifications of the present invention without departing fromthe spirit and scope of the appended claims.

1. An apparatus for capturing a desired quantity of material from asample suspension on a filter, comprising: a body member defining achamber and having opposed ends, an outlet port in one of said ends, andan inlet port; said inlet port and said outlet port defining a singlepathway for sample suspension to flow though said apparatus; asubstantially planar filter mounted within said chamber between saidinlet port and said outlet port and completely across said singlepathway, so that sample suspension flowing through said apparatus mustflow from said inlet port through said filter and to said outlet port;said filter being deformable toward said outlet end at a predeterminedpressure change across said filter and having a first porous portion anda second porous portion concentrically arranged centrally of said firstportion, said predetermined pressure change selected so that when adesired quantity of material has been captured by said first portion,said substantially planar filter deforms against said outlet end suchthat all flow of sample suspension through said apparatus must flowthrough said more restrictive second portion; and means for providing apressure to cause said sample suspension to flow through said apparatus.